Long-Term In Vivo Gene Expression via Delivery of PEI–DNA Condensates from Porous Polymer Scaffolds
dc.contributor.author | Huang, Yen-Chen | en_US |
dc.contributor.author | Riddle, Kathryn W. | en_US |
dc.contributor.author | Rice, Kevin G. | en_US |
dc.contributor.author | Mooney, David J. | en_US |
dc.date.accessioned | 2009-07-10T19:06:58Z | |
dc.date.available | 2009-07-10T19:06:58Z | |
dc.date.issued | 2005-05-01 | en_US |
dc.identifier.citation | Huang, Yen-Chen; Riddle, Kathryn; Rice, Kevin G.; Mooney, David J. (2005). "Long-Term In Vivo Gene Expression via Delivery of PEI–DNA Condensates from Porous Polymer Scaffolds." Human Gene Therapy 16(5): 609-617 <http://hdl.handle.net/2027.42/63281> | en_US |
dc.identifier.uri | https://hdl.handle.net/2027.42/63281 | |
dc.identifier.uri | http://www.ncbi.nlm.nih.gov/sites/entrez?cmd=retrieve&db=pubmed&list_uids=15916485&dopt=citation | en_US |
dc.description.abstract | Nonviral delivery vectors are attractive for gene therapy approaches in tissue engineering, but suffer from low transfection efficiency and short-term gene expression. We hypothesized that the sustained delivery of poly(ethylenimine) (PEI)-condensed DNA from three-dimensional biodegradable scaffolds that encourage cell infiltration could greatly enhance gene expression. To test this hypothesis, a PEI-condensed plasmid encoding β-galactosidase was incorporated into porous poly(lactide-co-glycolide) (PLG) scaffolds, using a gas foaming process. Four conditions were examined: condensed DNA and uncondensed DNA encapsulated into PLG scaffolds, blank scaffolds, and bolus delivery of condensed DNA in combination with implantation of PLG scaffolds. Implantation of scaffolds incorporating condensed β-galactosidase plasmid into the subcutaneous tissue of rats resulted in a high level of gene expression for the entire 15-week duration of the experiment, as exemplified by extensive positive staining for β-galactosidase gene expression observed on the exterior surface and throughout the cross-sections of the explanted scaffolds. No positive staining could be observed for the control conditions either on the exterior surface or in the cross-section at 8- and 15-week time points. In addition, a high percentage (55–60%) of cells within scaffolds incorporating condensed DNA at 15 weeks demonstrated expression of the DNA, confirming the sustained uptake and expression of the encapsulated plasmid DNA. Quantitative analysis of β-galactosidase gene expression revealed that expression levels in scaffolds incorporating condensed DNA were one order of magnitude higher than those of other conditions at the 2- week time point and nearly two orders of magnitude higher than those of the control conditions at the 8- and 15-week time points. This study demonstrated that the sustained delivery of PEI–condensed plasmid DNA from PLG scaffolds led to an in vivo long-term and high level of gene expression, and this system may find application in areas such as bone tissue engineering. | en_US |
dc.format.extent | 338191 bytes | |
dc.format.extent | 2489 bytes | |
dc.format.mimetype | application/pdf | |
dc.format.mimetype | text/plain | |
dc.publisher | Mary Ann Liebert, Inc., publishers | en_US |
dc.title | Long-Term In Vivo Gene Expression via Delivery of PEI–DNA Condensates from Porous Polymer Scaffolds | en_US |
dc.type | Article | en_US |
dc.subject.hlbtoplevel | Health Sciences | en_US |
dc.description.peerreviewed | Peer Reviewed | en_US |
dc.identifier.pmid | 15916485 | en_US |
dc.description.bitstreamurl | http://deepblue.lib.umich.edu/bitstream/2027.42/63281/1/hum.2005.16.609.pdf | |
dc.identifier.doi | doi:10.1089/hum.2005.16.609 | en_US |
dc.identifier.source | Human Gene Therapy | en_US |
dc.identifier.source | Human Gene Therapy | en_US |
dc.owningcollname | Interdisciplinary and Peer-Reviewed |
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